Testing an Immunotherapy Anti-cancer Drug, Nivolumab, for Advanced Cancers in Patients With Autoimmune Disorders, AIM-NIVO
Start Date
7/16/2019
Completion Date
3/30/2028
Summary
This phase Ib trial studies the side effects of nivolumab and to see how well it works alone and in combination with other treatments, such as ipilimumab, cabozantinib, platinum containing therapy, and fluoropyrimidine, in treating patients with autoimmune disorders and cancer that has spread from where it first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced), to other places in the body (metastatic) or cannot removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib blocks certain proteins, which may help keep tumor cells from growing. It may also prevent the growth of new blood vessels that tumors need to grow. Cabozantinib is a type of tyrosine kinase inhibitor and a type of angiogenesis inhibitor. Chemotherapy drugs, such as platinum containing therapies and fluoropyrimidine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab alone and in combination with other treatments, including ipilimumab, cabozantinib, platinum containing therapy, or fluoropyrimidine, may be safe, tolerable, and/or effective in treating patients with autoimmune disorders and advanced, metastatic, or unresectable cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the overall safety, and toxicities associated with the use of the anti-programmed death 1 (PD-1) antibody nivolumab in patients with varying severity of dermatomyositis (DM)/systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) (ulcerative colitis \[UC\] and Crohn's disease \[CD\]), multiple sclerosis (MS), Sjogren's syndrome \[SjS\], psoriasis (PsO)/psoriatic arthritis (PsA), and other autoimmune diseases. II. To assess the overall safety, and toxicities associated with the use of the anti-programmed death 1 (PD-1) antibody nivolumab and other Food and Drug Administration (FDA)-approved combinations for given oncologic indications in patients with varying severity of DM/SSc, RA, SLE, IBD (ulcerative colitis \[UC\] and Crohn's disease \[CD\]), MS, Sjogren's syndrome \[SjS\], psoriasis (PsO)/psoriatic arthritis (PsA), and other autoimmune diseases. SECONDARY OBJECTIVES: I. To evaluate the efficacy of nivolumab in terms of objective response rates (ORRs), progression-free survival (PFS), and overall survival (OS) in patients with cancer and DM/SSc, RA, SLE, IBD (UC and CD), MS, SjS, PsO/PsA, and other autoimmune diseases. II. To observe and record anti-tumor activity. III. To propose dosing recommendations for anti-PD-1 antibodies based on the severity of the autoimmune disorder. IV. To evaluate the impact of nivolumab on the disease severity indices for: DM/SSc, RA, SLE, IBD: UC and CD, not specified (NS), MS, SjS, PsO/PsA. V. To identify biomarkers of response and toxicity. OUTLINE: Patients are assigned to 1 of 11 arms. ARM I (MONOTHERAPY): Patients may receive single agent nivolumab intravenously (IV) over 30 minutes every 4 weeks for up to 2 years for patients with metastatic indications, for up to 1 year for adjuvant indications or for up to 3 months after surgery for neoadjuvant indications in the absence of disease progression or unacceptable toxicity. ARM II (UNRESECTABLE OR METASTATIC MELANOMA): Patients receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab may continue every 4 weeks in the absence of disease progression or unacceptable toxicity. ARM III (NEOADJUVANT TREATMENT OF RESECTABLE NON-SMALL CELL LUNG CANCER \[NSCLC\]): Patients receive nivolumab IV over 30 minutes in combination with platinum doublet therapy every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. ARM IV (METASTATIC PD-L1 POSITIVE NSCLC): Patients receive nivolumab IV over 30 minutes every 3 weeks and ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM V (METASTATIC OR RECURRENT NSCLC): Patients receive nivolumab IV over 30 minutes every 3 weeks, ipilimumab IV every 6 weeks and platinum doublet therapy every 3 weeks for up to 2 cycles of combination therapy. Treatment with nivolumab and ipilimumab repeats for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM VI (MALIGNANT PLEURAL MESOTHELIOMA): Patients receive nivolumab IV over 30 minutes every 3 weeks and ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM VII (ADVANCED RENAL CELL CARCINOMA \[RCC\]): Patients receive nivolumab IV over 30 minutes in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity. Patients may optionally receive nivolumab IV every 2 or 4 weeks in combination with cabozantinib orally (PO) once daily (QD) for up to 2 years of combination therapy in the absence of disease progression or unacceptable toxicity. Treatment with single agent cabozantinib may continue in the absence of disease progression or unacceptable toxicity. ARM VIII (MICROSATELLITE INSTABILITY-HIGH \[MSI-H\] OR MISMATCH REPAIR DEFICIENT \[dMMR\] METASTATIC COLORECTAL CANCER): Patient receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity. ARM IX (HEPATOCELLULAR CARCINOMA \[HCC\]): Patients receive nivolumab IV over 30 minutes in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity. ARM X (ESOPHAGEAL SQUAMOUS CELL CARCINOMA): Patients receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with fluoropyrimidine and platinum-containing chemotherapy for up to 2 years in the absence of disease progression or unacceptable toxicity OR receive nivolumab IV every 2 or 3 weeks in combination with ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may then continue receiving fluoropyrimidine and platinum-containing chemotherapy in the absence of disease progression or unacceptable toxicity. ARM XI (GASTRIC CANCER, GASTROESOPHAGEAL JUNCTION CANCER, AND ESOPHAGEAL ADENOCARCINOMA): Patients receive nivolumab IV over 30 minutes in combination with fluoropyrimidine and platinum-containing chemotherapy every 2 or 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, cerebrospinal fluid (CSF), tissue, stool, and urine samples throughout the trial. After completion of study treatment, patients without disease progression are followed for 100 days, and patients with disease progression are followed every 12 weeks for up to 5 years.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Biospecimen Collection
Cabozantinib
Fluoropyrimidine
Ipilimumab
Nivolumab
Platinum Compound
Platinum Doublet
Conditions
Locations
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233
United States
Stanford Cancer Institute Palo Alto
Palo Alto, California 94304
United States
University of California Davis Comprehensive Cancer Center
Sacramento, California 95817
United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut 06510
United States
Yale University
New Haven, Connecticut 06520
United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia 20007
United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322
United States
Northwestern University
Chicago, Illinois 60611
United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois 60637
United States
University of Kansas Clinical Research Center
Fairway, Kansas 66205
United States
HaysMed
Hays, Kansas 67601
United States
University of Kansas Cancer Center
Kansas City, Kansas 66160
United States
Lawrence Memorial Hospital
Lawrence, Kansas 66044
United States
The University of Kansas Cancer Center - Olathe
Olathe, Kansas 66061
United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas 66210
United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas 66211
United States
Mercy Hospital Pittsburg
Pittsburg, Kansas 66762
United States
Salina Regional Health Center
Salina, Kansas 67401
United States
University of Kansas Health System Saint Francis Campus
Topeka, Kansas 66606
United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536
United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287
United States
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland 20892
United States
National Institutes of Health Clinical Center
Bethesda, Maryland 20892
United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts 02114
United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri 63376
United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141
United States
University Health Truman Medical Center
Kansas City, Missouri 64108
United States
University of Kansas Cancer Center - North
Kansas City, Missouri 64154
United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri 64064
United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri 64116
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Siteman Cancer Center-South County
St Louis, Missouri 63129
United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri 63136
United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey 08903
United States
NYU Langone Hospital - Long Island
Mineola, New York 11501
United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016
United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York 10032
United States
NYP/Weill Cornell Medical Center
New York, New York 10065
United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107
United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232
United States
UT Southwestern Simmons Cancer Center - RedBird
Dallas, Texas 75237
United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas 75390
United States
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth, Texas 76104
United States
UT MD Anderson Cancer Center
Houston, Texas 77030
United States
UT Southwestern Clinical Center at Richardson/Plano
Richardson, Texas 75080
United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah 84112
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia 23298
United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario M5G 2M9
Canada